Combination

Abstract

The present invention provides a combination comprising at least two of the following: (i) an insulin modulator, (ii) an immunosuppressive agent and (iii) an aldosterone antagonist, for instance a combination comprising at least two of (i) exenatide, or a functional derivative or analog thereof, or a pharmaceutically acceptable salt thereof; (ii) cyclosporine, or a functional derivative or analog thereof, or a pharmaceutically acceptable salt thereof; and (iii) potassium canrenoate, or a functional derivative or analog thereof. Said combinations are suitable for cardioprotection and for treating and/or preventing ischemia and/or reperfusion injury. Further aspects of the invention relate to pharmaceutical products and pharmaceutical compositions comprising said combinations according to the invention, and methods of treatment using the same.

What is claimed is: 
     
       1. A method of treating ischemia or reperfusion injury, said method consisting of simultaneously or sequentially administering to a subject in need thereof a pharmaceutical composition consisting of exenatide or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, and a pharmaceutical composition consisting of potassium canrenoate, and a pharmaceutically acceptable carrier, diluent or excipient, and wherein exenatide is administered at a dose in the range from about 0.05 to about 0.15 μg/kg and potassium canrenoate is administered at a dose in the range from about 1 to about 3 mg/kg, wherein the pharmaceutical compositions are administered parenterally. 
     
     
       2. The method according to  claim 1 , wherein the ischemia or reperfusion injury is ischemia or reperfusion injury of the brain, heart, lung, or kidney. 
     
     
       3. The method according to  claim 1 , wherein the pharmaceutical compositions are administered before reperfusion. 
     
     
       4. The method according to  claim 1 , wherein the pharmaceutical compositions are administered simultaneously to said subject. 
     
     
       5. The method according to  claim 1 , wherein the pharmaceutical compositions are administered sequentially. 
     
     
       6. The method according to  claim 1 , wherein the ischemia is myocardial ischemia. 
     
     
       7. The method according to  claim 1 , wherein the reperfusion injury is myocardial reperfusion injury or acute myocardial infarction. 
     
     
       8. The method according to  claim 1 , wherein the pharmaceutical compositions are administered intravenously. 
     
     
       9. The method according to  claim 1 , wherein the potassium canrenoate is administered at a dose of about 1 mg/kg. 
     
     
       10. The method according to  claim 1 , wherein the potassium canrenoate is administered at a dose of about 1 mg/kg, and the exenatide is administered at a dose of about 0.05 μg/kg. 
     
     
       11. A method of treating ischemia or reperfusion injury, said method consisting of administering to a subject in need thereof a pharmaceutical composition consisting of exenatide, or a pharmaceutically acceptable salt thereof, potassium canrenoate, and a pharmaceutically acceptable carrier, diluent or excipient, and wherein exenatide is administered at a dose in the range from about 0.05 to about 0.15 μg/kg and potassium canrenoate is administered at a dose in the range from about 1 to about 3 mg/kg, wherein the exenatide and potassium canrenoate are administered parenterally. 
     
     
       12. The method according to  claim 11 , wherein the potassium canrenoate is administered at a dose of about 1 mg/kg. 
     
     
       13. The method according to  claim 11 , wherein the potassium canrenoate is administered at a dose of about 1 mg/kg, and the exenatide is administered at a dose of about 0.05 μg/kg. 
     
     
       14. A method of treating ischemia or reperfusion injury, said method consisting of simultaneously or sequentially administering to a subject in need thereof exenatide, or a pharmaceutically acceptable salt thereof, and potassium canrenoate, and wherein exenatide is administered at a dose in the range from about 0.05 to about 0.15 μg/kg and potassium canrenoate is administered at a dose in the range from about 1 to about 3 mg/kg, wherein the exenatide and potassium canrenoate are administered parenterally. 
     
     
       15. The method according to  claim 11  or  14 , wherein the exenatide and potassium canrenoate are administered intravenously before reperfusion. 
     
     
       16. The method according to  claim 11  or  14 , wherein the ischemia is myocardial ischemia. 
     
     
       17. The method according to  claim 11  or  14 , wherein the reperfusion injury is myocardial reperfusion injury or acute myocardial infarction. 
     
     
       18. The method according to  claim 14 , wherein the exenatide and potassium canrenoate are administered simultaneously. 
     
     
       19. The method according to  claim 14 , wherein the exenatide and potassium canrenoate are administered sequentially. 
     
     
       20. The method according to  claim 14 , wherein the potassium canrenoate is administered at a dose of about 1 mg/kg. 
     
     
       21. The method according to  claim 14 , wherein the potassium canrenoate is administered at a dose of about 1 mg/kg, and the exenatide is administered at a dose of about 0.05 μg/kg.